This project is designed to investigate the kinetic behavior of tumor cell-biologic marker interactions before and during therapy, utilizing both experimental and analytical (computer simulation) techniques, including the following: 1) the quantitative analysis of the dynamics of multiple marker distribution patterns for patients with advanced malignancies before and after therapy and its utility to assess the disease course of the patients during therapy; 2) to estimate, by measuring the concentrations of the biologic markers in the body fluids of the patients, the number of tumor cells via a quantitative model that integrates cell kinetics with the synthesis of biologic markers by tumors; 3) the time-course behavior of antitumor drug perturbation of the cell age, cell size, and DNA content distributions in relation to the synthesis of biologic marker and implications for the optimal design of antitumor drug schedules for cancer therapy.